The overall objective of this project is to examine the metabolism of albumin and total cellular mRNA in the diabetic rat liver. Diabetes results in a significant decrease in the production of albumin and other secretory proteins of the liver. This reduction in protein synthetic activity appears to be associated with alterations in mRNA metabolism. Administration of insulin appears to restore these metabolic defects to normal, but the molecular nature of the involvement of this hormone is unknown. The molecular events that occur between RNA transcription and translation are attractive candidates for regulation during the cellular metabolic alterations that occur in diabetes and insulin therapy. In this project, the intracellular distribution of specific mRNA sequences will be examined in the diabetic and insulin-treated rat liver. The production and utilization of mRNAs will be related to the protein synthetic capacity of the liver and isolated hepatocytes. The molecular mechanism by which insulin modulates these post-transcriptional events will be investigated.